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Immunotherapy for Breast Cancer

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  • Breast Cancer
  • Treatment Options
  • CRI's Impact
  • Clinical Trials

How is Immunotherapy Changing the Outlook for Patients with Breast Cancer?

Reviewed By: Leisha A. Emens, M.D., Ph.D.
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Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD
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Breast cancer is one of the most commonly diagnosed cancer types among women globally. In the United States alone, there were an estimated 255,000 cases of breast cancer diagnosed in 2017 along with 41,000 deaths, and approximately 1 in 8 women and about 1 in 1,000 men will develop invasive breast cancer at some point in their lives. Thus, the need for effective, lasting breast cancer treatment is urgent.

Increased risk for breast cancer is associated with a personal or family history of the disease and inherited genetic mutations in breast cancer susceptibility genes. These include BRCA1 and BRCA2 and other less common inherited gene mutations. An inherited predisposition to develop breast cancer accounts for approximately 5%-10% of all breast cancer cases, but is rare in the general population (less than 1%). Women with BRCA1 and BRCA2 mutations have an estimated 45% to 65% higher risk of developing breast cancer by age 70, though the risk is highest around age 40. People with these mutations should discuss their risk with a genetic counsellor. Other known risk factors include obesity, use of MHT (a hormone therapy that combines progestin and estrogen), high breast tissue density, alcohol consumption, and physical inactivity.

Current methods for breast cancer treatment typically involve surgery if the disease is diagnosed early. Depending on the stage and molecular characteristics of the cancer when diagnosed, breast cancer surgery may be followed by additional chemotherapy, radiation, or targeted therapies, including hormone therapy.

Breast cancer has traditionally been regarded as immunologically silent (unresponsive to the immune system), though several newer preclinical and clinical studies now suggest that immunotherapy treatment has the potential to improve outcomes for breast cancer patients, and displays numerous advantages over more conventional chemotherapy-based treatments that directly target the tumor itself.

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Breast Cancer Treatment Options

Traditional treatments for breast cancer include chemotherapy, radiation, and surgery. Hormonal therapy, which can reduce levels of estrogen and progesterone, may also be used to prevent disease recurrence in women with hormone receptor-positive tumors.

There are currently three approved immunotherapy options for patients with tumors that overexpress a protein receptor called HER2 (HER2 3+, or FISH-positive).

Targeted Antibodies

  • Pertuzumab (Perjeta®): a monoclonal antibody that targets the HER2 pathway; approved for early-stage, HER2-positive breast cancer after surgery
  • Trastuzumab (Herceptin®): a monoclonal antibody that targets the HER2 pathway; approved for early-stage, HER2-positive breast cancer after surgery
  • Trastuzumab emtansine (Kadcyla®): an antibody-drug conjugate that targets the HER2 pathway and delivers toxic drugs to tumors; approved for subsets of patients with HER2-positive breast cancer

Although treatment with trastuzumab and other HER2-directed therapies are associated with significant efficacy, only patients with the highest levels of HER2 expression, representing approximately 20% of breast cancer patients, have the potential to respond. Moreover, many patients expressing high levels of HER2 progress or relapse despite receiving the best HER2-directed treatments, and thus require novel treatment approaches. Additionally for patients with ER+ or PR+ breast cancer who are refractory to endocrine therapy, or patients who have triple negative breast cancer, targeted therapeutic options remain quite limited. New therapeutic strategies for breast cancer are needed to improve clinical outcomes for breast cancer patients, particularly those with advanced disease. Other immunotherapies are currently being tested in breast cancer clinical trials and several have shown impressive results.

Because current treatments are unlikely to cure advanced breast cancer, patients in otherwise good health are encouraged to think about taking part in clinical trials. Go to our Clinical Trial Finder to find clinical trials of immunotherapies for breast cancer that are currently enrolling patients.

Find a Breast Cancer Clinical Trial

CRI's Impact in Breast Cancer

Our organization's commitment to breast cancer research and breast cancer immunotherapy goes back nearly four decades, when we first began to fund the New York Metropolitan Breast Cancer group—a coalition of physicians and surgeons from over 15 medical institutions working together to develop a coordinated breast cancer diagnosis and treatment program.

At the Cancer Research Institute, we’re invested in the promise of effective breast cancer immunotherapy treatment and are dedicated to developing lifesaving cures for all cancers. Some of CRI’s contributions to the immunological understanding and treatment of breast cancer include:

  • One of the first signs that breast cancer was subject to immunosurveillance and therefore could potentially benefit from approaches designed to induce or enhance anti-breast cancer immune responses, discovered by Maurice Black, M.D., a CRI-funded grantee at New York Medical College from 1983-1987.
  • One of the first to clone the HER2/neu oncogene, a key milestone enabling the development of trasuzumab and other HER2 directed therapies for HER2+ breast cancer, done by Mien-Chie Hung, Ph.D., a CRI Postdoctoral Fellow at the Whitehead Institute for Biomedical Research) from 1983 to 1986.
  • The synthetic double-stranded RNA known as Poly-ICLC is being tested as an adjuvant in several CRI-funded vaccine trials to determine its effect in boosting the anti-cancer immune response
  • Enhance T cell responses against tumors by using “smart” polymers to create a new type of cancer vaccine and to test this new strategy in a preclinical model of human breast cancer, developed by John T. Wilson, a CRI Postdoctoral Fellow at the University of Washington from 2011-2014.
  • Study of an immunosuppressive pathway that is activated in tumor-associated immune cells in breast cancer models, carried out by by Ming Li, Ph.D., a CRI CLIP Grantee at Memorial Sloan Kettering Cancer Center from 2012-2014.

You can explore CRI’s current research into breast cancer in our funding directory.

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Featured Patient

I thought, ‘What else can I do to help my daughters, my nieces?’

Diane Altenburg
Breast Cancer  |  Diagnosed
Read My Story
Featured Scientist
Nicholas David Huntington, Ph.D. and Sandra Nicholson, Ph.D.
Walter and Eliza Hall Institute of Medical Research (Australia)
CLIP Investigator  |  2016
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Breast Cancer Statistics

1 in 8 Women in the United States will develop breast cancer
12% Of all cancer diagnoses worldwide are breast cancer
89% Overall 5-year survival rate

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Breast Cancer Clinical Trials Targets

Therapies
  • Targeted Antibodies
  • Cancer Vaccines
  • Adoptive Cell Therapy
  • Immunomodulators
  • Oncolytic Virus Therapy

Targeted antibodies are proteins produced by the immune system that can be customized to target specific markers (known as antigens) on cancer cells, in order to disrupt cancerous activity, especially unrestrained growth. Antibody-drug conjugates (ADCs) are equipped with anti-cancer drugs that they can deliver to tumors. Bi-specific T cell-engaging antibodies (BiTEs) bind both cancer cells and T cells in order to help the immune system respond more quickly and effectively. Antibody targets under evaluation in breast cancer clinical trials include:

  • Angiopoietin: a protein that can promote blood vessel formation in tumors
  • DLL/Notch: a pathway that can promote cell growth
  • EGFR: a pathway that controls cell growth and is often mutated in cancer
  • HER2: a pathway that controls cell growth and is commonly overexpressed in breast cancer and is associated with metastasis, or disease spread
  • Mesothelin: a protein that’s commonly overexpressed in breast cancer and may aid metastasis
  • TROP2: a protein that’s commonly overexpressed in cancer and appears to aid  cancer cell self-renewal, proliferation, invasion, and survival
  • VEGF / VEGF-R: a pathway that, when targeted with treatment, can prevent tumor blood vessel formation

Cancer vaccines are designed to elicit an immune response against tumor-specific or tumor-associated antigens, encouraging the immune system to attack cancer cells bearing these antigens. Cancer vaccines can be made from a variety of components, including cells, proteins, DNA, viruses, bacteria, and small molecules. Cancer vaccine targets under evaluation in breast cancer clinical trials include:

  • HER2: a pathway that controls cell growth and is commonly overexpressed in breast cancer and is associated with metastasis, or disease spread
  • P53: a tumor suppressor protein that is often mutated, nonfunctional, and overexpressed in cancer
  • Personalized neoantigens: these abnormal proteins arise from mutations and are expressed exclusively by tumor cells
  • Ras: a central signaling protein that is commonly mutated in cancer and has been linked to abnormal growth and cell division
  • Survivin: a protein that can prevent cellular death and is overexpressed by a number of cancer cell types
  • Telomerase: an enzyme that helps maintain the health of cellular DNA; exploited by cancer cells to achieve immortality
  • Tumor-associated antigens (TAAs): proteins often expressed at abnormally high levels on tumor cells that can be used to target them; also found on normal cells at lower levels

Cell-based therapy, also referred to as adoptive cell therapy, takes a patient’s own immune cells, expands or otherwise modifies them, and then reintroduces them to the patient, where they can seek out and eliminate cancer cells. In CAR T cell therapy, T cells are modified and equipped with chimeric antigen receptors (CARs) that enable superior anti-cancer activity. Natural killer cells (NKs) and tumor infiltrating lymphocytes (TILs) can also be enhanced and reinfused in patients. Cell-based immunotherapy targets under evaluation in breast cancer clinical trials include:

  • CEA: a protein involved in cellular adhesion normally produced only before birth; often abnormally expressed in cancer and may contribute to metastasis
  • MAGE antigens: the genes that produce these proteins are normally turned off in adult cells, but de-regulated cancer cells often re-activate their expression
  • Mesothelin: a protein that is commonly overexpressed in cancer and may aid metastasis
  • NY-ESO-1: a protein that is normally produced only before birth, but is often abnormally expressed in cancer
  • ROR1: an enzyme that is normally produced only before birth, but is often abnormally expressed in cancer and may promote cancer cell migration as well as prevent cancer cell death

Immunomodulators manipulate the “brakes” and “gas pedals” of the immune system. Checkpoint inhibitors target molecules on immune cells to unleash new or enhance existing immune responses against cancer. Cytokines regulate immune cell maturation, growth, and responsiveness. Adjuvants can stimulate pathways to provide longer protection or produce more antibodies. Immunomodulator targets under evaluation in bladder cancer clinical trials include:

  • CD40: activating this co-stimulatory pathway can kickstart adaptive immune responses
  • CD47: this surface protein acts as a “don’t eat me!” signal that protects cancer from being consumed by certain immune cells; blocking CD47 can improve their cancer-eating activity
  • CD73 or A2AR: blocking these pathways can help prevent the production of immunosuppressive adenosine
  • CD137 (also known as 4-1BB): activating this co-stimulatory pathway can help promote the growth, survival, and activity of cancer-fighting T cells
  • CSF1/CSF1R: blocking this pathway can help reprogram cancer-supporting macrophages
  • CTLA-4: blocking this pathway can help promote expansion and diversification of cancer-fighting T cells
  • GITR: activating this pathway can help prevent immunosuppression and increase the survival of cancer-fighting T cells
  • IDO: blocking this enzyme’s activity can help prevent cancer-fighting T cells from being suppressed
  • IL-2/IL-2R: activating this cytokine pathway can help promote the growth and expansion of cancer-fighting T cells
  • LAG3: blocking this pathway may be able to help prevent suppression of cancer-fighting T cells
  • OX40: activating this co-stimulatory pathway can help promote T cell survival after activation
  • PD-1 / PD-L1: blocking this pathway can help prevent cancer-fighting T cells from becoming “exhausted”, and can restore the activity of already-exhausted T cells
  • STING: activating this protein in the DNA-sensing pathway can help stimulate immune responses against threats such as viruses and cancer
  • Toll-like receptors (TLRs): activation of these innate immune receptors can help stimulate vaccine-like responses against tumors

Oncolytic virus therapy uses modified viruses that can infect tumor cells and cause them to self-destruct. This can attract the attention of immune cells to eliminate the main tumor and potentially other tumors throughout the body. Viral platforms under evaluation in breast cancer clinical trials include:

  • Adenovirus: a family of common viruses that can cause a wide range of typically mild effects including sore throat, fatigue, and cold-like symptoms
  • Herpes simplex virus: a virus that can cause the formation of sores on the mouth and genitals
  • Maraba virus: a virus found exclusively in insects
  • Measles virus: a highly contagious virus that infects the respiratory tract and can cause measles
  • Reovirus: a family of viruses that can affect the gastrointestinal and respiratory tracts in a range of animal species
  • Vaccinia virus: the virus that was used to help vaccinate against and eliminate smallpox; rarely causes illness in humans and is associated with a rash covering the body
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Sources: National Cancer Institute; National Cancer Institute Physician Data Query (PDQ); American Cancer Society Facts & Figures 2016; GLOBOCAN 2012; GLOBOCAN 2018; NCI Surveillance Epidemiology and End Results (SEER); National Comprehensive Cancer Network (NCCN) Guidelines for Patients; ClinicalTrials.gov; breastcancer.org; CRI grantee progress reports and other CRI grantee documents

Updated October 2018

*Immunotherapy results may vary from patient to patient. Consult a healthcare professional about your treatment options.

*Immunotherapy results may vary from patient to patient.

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